JP6778809B2 - A method for producing a base for a patch and a method for producing a patch using a base obtained thereby. - Google Patents

Description

The present invention relates to a method for producing a base for a patch and a method for producing a patch using a base obtained by the method, and more particularly, a method for producing a base for a patch containing gelatin and polyvinyl alcohol and a method for producing the same. The present invention relates to a method for producing a patch using the obtained base.

The base for the patch contains water-soluble polymers such as gelatin, polyacrylic acid, polyacrylic acid salt, and polyvinyl alcohol in order to ensure the high water content of the base layer and excellent shape retention and cohesiveness. include. In addition, such a base for a patch contains a cooling agent such as L-menthol in order to exert a cooling effect (for example, International Publication No. 2006/090782 (Patent Document 1) and Patent Document 1). International Publication No. 2015/025935 (Patent Document 2)).

However, in the conventional base for patches, the strong pungent odor of L-menthol used as a refreshing agent may rarely become a problem, and as an odorless cooling agent instead of L-menthol, L -Menthol glyceryl ether is known, and a derivative thereof has also been proposed (for example, JP-A-9-217803 (Patent Document 3)).

International Publication No. 2006/090782 International Publication No. 2015/025935 Japanese Unexamined Patent Publication No. 9-217083

However, the present inventors have found that even if the refreshing agent is changed from L-menthol to L-menthylglyceryl ether in the conventional base for patches, an unpleasant odor is still generated.

The present invention has been made in view of the above-mentioned problems of the prior art, and even when L-menthylglyceryl ether is used as a cooling agent, it has an unpleasant odor while maintaining the adhesive strength of the base. It is an object of the present invention to provide a patch base for which the occurrence of the above is suppressed and a patch using the same.

As a result of intensive studies to achieve the above object, the present inventors have found that the cause of generating an unpleasant odor in a conventional patch base containing L-mentylglyceryl ether as a cooling agent is the base. By adding a poly (methyl acrylate / 2-ethylhexyl acrylate) copolymer to the base, an unpleasant odor generated from gelatin and polyvinyl alcohol can be obtained. It was found that it was suppressed, and the present invention was completed.

That is, the method for producing a base for a patch of the present invention is a method for producing a base containing gelatin, polyvinyl alcohol, a 2-ethylhexyl copolymer of methyl acrylate / acrylate, and L-menthylglyceryl ether. ,
With respect to the total mass of the base
The gelatin content is 1.5 to 6% by mass.
The content of the polyvinyl alcohol is 0.5 to 8% by mass.
So that the content of the methyl acrylate / 2-ethylhexyl acrylate copolymer is 0.5 to 13% by mass.
This is a method of mixing gelatin, polyvinyl alcohol, 2-ethylhexyl acrylate copolymer, and L-menthylglyceryl ether.

In such a method for producing a base for a patch of the present invention, it is preferable to further mix at least one pressure-sensitive adhesive selected from the group consisting of polyacrylic acid and a neutralized polyacrylic acid.

Further, the method for producing a patch of the present invention is a method for producing a patch having a plaster layer containing a base and a drug on a support.
The base is prepared by the method for producing a base for a patch of the present invention, the plaster layer containing the base and the drug is formed, and the support is laminated on the plaster layer. The method. In such a method for producing a patch of the present invention, a plaster containing the base and the drug is prepared, and the plaster is spread on a release liner to form the plaster layer. It is preferable to do so.

According to the present invention, even when L-menthylglyceryl ether is used as a cooling agent, a patch base and a patch base in which the generation of an unpleasant odor is suppressed while maintaining the adhesive strength of the base. It becomes possible to provide a patch using the above.

Hereinafter, the present invention will be described in detail according to its preferred embodiment.

First, a method for producing a base for a patch of the present invention will be described. The method for producing a base for a patch of the present invention is a method for producing a base containing gelatin, polyvinyl alcohol, a 2-ethylhexyl copolymer of methyl acrylate / 2-ethylhexyl acrylate, and L-menthylglyceryl ether.
With respect to the total mass of the base
The gelatin content is 1.5 to 6% by mass.
The content of the polyvinyl alcohol is 0.5 to 8% by mass.
So that the content of the methyl acrylate / 2-ethylhexyl acrylate copolymer is 0.5 to 13.0% by mass.
This is a method of mixing gelatin, polyvinyl alcohol, 2-ethylhexyl acrylate copolymer, and L-menthylglyceryl ether.

The gelatin used in the present invention is not particularly limited as long as it is generally used as a patch. In the patch base obtained by the present invention, the content of this gelatin is 1.5 to 6% by mass with respect to the total mass of the base. When the gelatin content is less than 1.5% by mass, the unpleasant odor derived from gelatin does not occur even if the methyl acrylate / 2-ethylhexyl acrylate copolymer is not added to the base. Therefore, when a methyl acrylate / 2-ethylhexyl acrylate copolymer is added to the base for the purpose of suppressing the generation of an unpleasant odor derived from gelatin, the gelatin content is 1.5% by mass. It is necessary to target a base of% or more (preferably 2% by mass or more). On the other hand, when the gelatin content exceeds 6% by mass, the adhesive strength of the base is lowered. Further, from the viewpoint of sufficiently ensuring the adhesive strength of the base, the upper limit of the gelatin content is preferably 5% by mass or less, more preferably 4% by mass or less.

The polyvinyl alcohol used in the present invention is not particularly limited as long as it is generally used as a patch. In the patch base obtained by the present invention, the content of this polyvinyl alcohol is 0.5 to 8% by mass with respect to the total mass of the base. When the content of polyvinyl alcohol is less than 0.5% by mass, the unpleasant odor derived from polyvinyl alcohol does not occur even if the methyl acrylate / 2-ethylhexyl acrylate copolymer is not added to the base. Therefore, when a methyl acrylate / 2-ethylhexyl acrylate copolymer is blended as a base for the purpose of suppressing the generation of an unpleasant odor derived from polyvinyl alcohol, the content of polyvinyl alcohol is 0. It is necessary to target a base of 5% by mass or more (preferably 1% by mass or more). On the other hand, if the content of polyvinyl alcohol exceeds 8% by mass, the adhesive strength of the base becomes too high, and pain at the time of peeling cannot be tolerated. Further, from the viewpoint of ensuring an appropriate adhesive force that can tolerate pain at the time of peeling, the content of polyvinyl alcohol is preferably 7.5% by mass or less.

The methyl acrylate / 2-ethylhexyl acrylate copolymer used in the present invention is a copolymer of methyl acrylate and 2-ethylhexyl acrylate. By blending this methyl acrylate / 2-ethylhexyl acrylate copolymer, the generation of an unpleasant odor derived from gelatin and polyvinyl alcohol can be suppressed. In the base for a patch obtained by the present invention, the content of such a methyl acrylate / 2-ethylhexyl acrylate copolymer is 0.5 to 13% by mass with respect to the total mass of the base. When the content of the methyl acrylate / 2-ethylhexyl acrylate copolymer is less than 0.5% by mass, the generation of an unpleasant odor derived from gelatin and polyvinyl alcohol cannot be suppressed. On the other hand, when the content of the methyl acrylate / 2-ethylhexyl acrylate copolymer exceeds 13% by mass, the odor of the methyl acrylate / 2-ethylhexyl acrylate copolymer itself is generated. Further, from the viewpoint of surely suppressing the generation of unpleasant odors derived from gelatin and polyvinyl alcohol and the odors of the methyl acrylate / 2-ethylhexyl acrylate copolymer itself, the copolymer weight of methyl acrylate / 2-ethylhexyl acrylate. The content of the coalescence is preferably 0.6 to 12% by mass, more preferably 0.6 to 10% by mass.

In the present invention, the methyl acrylate / 2-ethylhexyl acrylate copolymer is preferably blended in the form of an aqueous emulsion dispersed in water at the time of producing a base for a patch. In this case, the solid content of the emulsion of the methyl acrylate / 2-ethylhexyl acrylate copolymer is the content of the methyl acrylate / 2-ethylhexyl acrylate copolymer used in the present invention. The aqueous emulsion of such a methyl acrylate / 2-ethylhexyl acrylate copolymer further contains a surfactant and / or a protective colloidal agent in addition to water and a 2-ethylhexyl acrylate copolymer. As the surfactant and / or protective colloidal agent, poly (oxyethylene) nonylphenyl ether is preferable. Therefore, the base for the patch obtained by the present invention may further contain a surfactant and / or a protective colloidal agent derived from the aqueous emulsion. When the surfactant and / or protective colloidal agent (preferably poly (oxyethylene) nonylphenyl ether) is further contained, the total content thereof is 0.01 to 0. With respect to the total mass of the base. 5% by mass is preferable.

The patch base obtained by the present invention contains L-menthylglyceryl ether as a cooling agent. The L-mentyl glyceryl ether is not particularly limited as long as it is generally used as a patch. Since this L-menthylglyceryl ether is odorless, a pungent odor like L-menthol is not generated from the base for a patch obtained by the present invention and a patch using the same. In the patch base obtained by the present invention, the content of the L-menthylglyceryl ether is preferably 0.5 to 7% by mass with respect to the total mass of the base.

Further, it is preferable that the base for a patch obtained by the present invention further contains at least one pressure-sensitive adhesive selected from the group consisting of polyacrylic acid and a neutralized polyacrylic acid. This improves the adhesive strength of the base.

The polyacrylic acid is not particularly limited as long as it is generally used as a patch. In the patch base obtained by the present invention, the content of this polyacrylic acid is preferably 1 to 5% by mass with respect to the total mass of the base. As a result, the adhesive strength of the base tends to be improved, the moldability and shape retention of the plaster layer tend to be improved, the hardness of the plaster layer is less likely to increase, and the adhesion to the skin is improved. There is a tendency.

The neutralized polyacrylic acid is not particularly limited as long as it is generally used as a patch, and examples thereof include polyacrylates such as sodium salt, potassium salt, calcium salt, and ammonium salt. Such a neutralized polyacrylic acid may be a partially neutralized product, a completely neutralized product, or a mixture thereof, but from the viewpoint of further improving the adhesive strength of the base. , A partially neutralized product of polyacrylic acid is preferable. In this partially neutralized product of polyacrylic acid, structural units derived from acrylic acid and structural units derived from acrylate are present in an arbitrary ratio in one polymer chain, and one polymer chain is present. It is preferable that 20 mol% or more of the carboxy groups in the medium are neutralized. The content of the neutralized polyacrylic acid is preferably 1 to 5% by mass with respect to the total mass of the base. As a result, the adhesive strength of the base is improved, and the moldability and shape retention of the plaster layer tend to be improved.

When the patch obtained by the present invention is a poultice, the base for the patch obtained by the present invention contains water (purified water). The water content is preferably 20 to 95% by mass, more preferably 25 to 90% by mass, based on the total mass of the base. As a result, the adhesive strength of the polyacrylic acid and the neutralized polyacrylic acid is sufficiently secured.

Further, the base for the patch obtained by the present invention includes a solubilizing agent, a moisturizer, a stabilizer, an inorganic powder, a coloring agent, a fragrance, a pH adjuster, etc. Various additives may be contained.

Next, the method for producing the patch of the present invention will be described. The method for producing a patch of the present invention is a method for producing a patch having a plaster layer containing a base and a drug on a support.
The base is prepared by the method for producing a base for a patch of the present invention, the plaster layer containing the base and the drug is formed, and the support is laminated on the plaster layer. The method.

The support is not particularly limited as long as it is generally used as a patch, and examples thereof include woven fabrics (knitted fabrics and the like), non-woven fabrics, resin films, foam sheets, and papers. The material of the woven fabric, the non-woven fabric, and the resin film is not particularly limited, and examples thereof include polyolefins such as polyethylene, polypropylene, and polybutylene; polyesters such as polyethylene terephthalate; rayon, polyurethane, and cotton.

In the patch obtained by the present invention, a plaster containing a base and a drug (pharmacologically active substance) obtained by the method for producing a base for a patch of the present invention on at least one surface of the support. Layers are formed. The drug is not particularly limited as long as it is generally used as a patch, and is, for example, a non-steroidal anti-inflammatory agent such as fervinac, flurbiprofen, diclofenac, diclofenac sodium, methyl salicylate, glycol salicylate, indomethacin, and ketoprofen. Alternatively, these esters, antihistamines such as difenhydramine, analgesics such as aspirin, acetaminophen, ibuprofen, and sodium loxoprofen, local anesthetics such as lidocaine, muscle relaxants such as schisametonium chloride, antifungal agents such as clotrimazole, and clonidine. Antihypertensive agents such as, nitroglycerin, vasodilators such as isosorbide nitrate, vitamins such as vitamin A, vitamin E (tocopherol), tocopherol acetate, vitamin K, octothiamine, riboflavin butyrate; prostaglandins, scopolamine, etc. Examples include fentanyl, indomethacin extract, and nonylate vanillylamide.

Further, in the patch obtained by the present invention, a release liner may be provided on the surface of the plaster layer opposite to the support. This release liner coats and protects the plaster layer. The peeling liner is not particularly limited as long as it is generally used as a patch, and for example, polyester (polyethylene terephthalate, polybutylene terephthalate, polyethylene naphthalate, etc.), polyolefin (polyethylene, polypropylene, polybutylene, etc.), etc. Resin film; examples include paper.

The method for producing the patch of the present invention is not particularly limited, and a general method for producing the patch can be adopted. For example, a plaster containing the base and the drug obtained by the method for producing a base for a patch of the present invention is prepared, the plaster is uniformly spread on a release liner, and then the support is laminated. As a result, a patch having the plaster layer on the support can be obtained.

Hereinafter, the present invention will be described in more detail based on Examples and Comparative Examples, but the present invention is not limited to the following Examples.

(Test Example 1)
1 to 5 parts by mass of gelatin was added to 99 to 95 parts by mass of purified water and dissolved to prepare a sample solution having a total amount of 100 parts by mass. A sensory test was performed on this sample solution, and the odor was evaluated between 0 and 100 based on the following criteria. This sensory test was performed on 5 subjects, and the average value of the odor score was calculated. The results are shown in Table 1.
[Criteria]
100: I feel very uncomfortable.
75: I feel uncomfortable.
50: Feels but not unpleasant.
25: I feel a little.
0: I don't feel it.

(Test Example 2)
A sensory test was conducted on 5 subjects in the same manner as in Test Example 1 except that polyvinyl alcohol (PVA) was used instead of gelatin, and the average value of the odor score was calculated. The results are shown in Table 1.

(Test Example 3)
A sensory test was conducted on 5 subjects in the same manner as in Test Example 1 except that polyacrylic acid (PAA) was used instead of gelatin, and the average value of the odor score was calculated. The results are shown in Table 1.

As shown in Table 1, gelatin and polyvinyl alcohol were found to be odor-causing substances. It was also found that when the contents of gelatin and polyvinyl alcohol were 2% by mass or more and 1% by mass or more, respectively, it felt unpleasant.

(Example 1)
First, 2 parts by mass of gelatin, 1 part by mass of polyvinyl alcohol (PVA), and 0.6 parts by mass (solid) of methyl acrylate / 2-ethylhexyl acrylate copolymer emulsion ("Nicazole TS-620" manufactured by Nippon Carbide Industries, Ltd.). Material standard), 1 part by mass of L-menthylglyceryl ether, 1 part by mass of sodium polyacrylate (PANA), 0.1 part by mass of magnesium silicate, and 94.3 parts by mass of purified water are mixed and stirred, and the base is used. Was prepared.

The obtained base was uniformly spread on the release liner so as to be 7 g per one poultice (140 mm × 100 mm). A support was immediately laminated on the support to obtain a poultice.

(Examples 2 to 16)
The base was prepared in the same manner as in Example 1 except that the amounts of gelatin, polyvinyl alcohol (PVA), methyl acrylate / 2-ethylhexyl acrylate copolymer emulsion, and purified water were changed to the amounts shown in Table 2. It was prepared and a poultice was prepared.

(Comparative Example 1)
A base was prepared in the same manner as in Example 4 except that 12 parts by mass of aminoalkyl methacrylate copolymer E (“Eudragit EPO” manufactured by Ebonic) was used instead of the methyl acrylate / 2-ethylhexyl acrylate copolymer emulsion. , Further, a poultice was prepared.

(Comparative Example 2)
Base in the same manner as in Example 4 except that 12 parts by mass of butyl methacrylate-methyl methacrylate copolymer (“Plastoid B” manufactured by Evonik Industries, Inc.) was used instead of the methyl acrylate / 2-ethylhexyl acrylate copolymer emulsion. Was prepared, and a poultice was further prepared.

(Comparative Examples 3 to 13)
The base was prepared in the same manner as in Example 1 except that the amounts of gelatin, polyvinyl alcohol (PVA), methyl acrylate / 2-ethylhexyl acrylate copolymer emulsion, and purified water were changed to the amounts shown in Table 3. It was prepared and a poultice was prepared.

<Adhesiveness test>
The obtained poultice was cut out into a rectangle of 25 mm × 90 mm and placed on a horizontal bottom under an inclined table composed of a sine curve, and a release liner was removed to expose the base layer. Next, a No. 17 steel ball (diameter: 17/32 inch) was rolled on the inclined surface of the inclined table, and the distance (stop distance) until the steel ball stopped on the surface of the base layer was measured. This measurement was repeated 3 times, and the average value (unit: mm) was calculated. The results are shown in Tables 4 to 7. In addition, when the steel ball did not stop on the surface of the base layer, it was described as "90 <". It is judged that the shorter the stopping distance is, the higher the adhesive strength of the base layer is, and if the stopping distance is 90 mm or less, the adhesive strength is acceptable as a preparation. However, if the stopping distance is too short, the adhesive strength becomes too strong and pain at the time of peeling cannot be tolerated. Therefore, the stopping distance is preferably 20 mm or more.

<Sensory test>
The obtained poultice was subjected to a sensory test and evaluated as an odor score between 0 and 100 based on the following criteria. This sensory test was performed on 5 subjects, and the average value of the odor score was calculated. The results are shown in Tables 4 to 7. The sensory test was not carried out when the result of the adhesiveness test was "90 <" or less than 20 mm.
[Criteria]
100: I feel very uncomfortable.
75: I feel uncomfortable.
50: Feels but not unpleasant.
25: I feel a little.
0: I don't feel it.

As is clear from the results shown in Table 4, the formulation odor derived from gelatin and PVA can be masked by using the methyl acrylate / 2-ethylhexyl acrylate copolymer emulsion (Example 4) (odor score 50). The following) was confirmed. On the other hand, when aminoalkyl methacrylate copolymer E (Comparative Example 1) or butyl methacrylate-methyl methacrylate copolymer (Comparative Example 2) is used instead of the methyl acrylate / 2-ethylhexyl acrylate copolymer emulsion, the preparation is prepared. The odor could not be masked (odor score exceeded 50).

As is clear from the results shown in Table 5, the content (based on solid matter) of the methyl acrylate / 2-ethylhexyl acrylate copolymer emulsion is 0.5 to 13.0 mass with respect to the total mass of the base. By setting the content within the range of% (Examples 1 to 4, 6 to 10 and 12 to 16), the odor of the formulation derived from gelatin and PVA can be masked (odor score of 50 or less), and the adhesive strength is acceptable as the formulation. It was confirmed that (stop distance 20 to 90 mm) can be obtained. On the other hand, when the content (based on solid matter) of the methyl acrylate / 2-ethylhexyl acrylate copolymer emulsion is less than 0.5% by mass (Comparative Examples 3, 5 and 10), the odor of the preparation can be masked. No (smell score exceeded 50). Further, when the content (based on solid matter) of the methyl acrylate / 2-ethylhexyl acrylate copolymer emulsion is 15.0% by mass (Comparative Example 4), the methyl acrylate / 2-ethylhexyl acrylate copolymer itself It was found that the odor of (odor score exceeded 50) was generated.

As is clear from the results shown in Table 6, gelatin is used as a base having a content of methyl acrylate / 2-ethylhexyl acrylate copolymer emulsion (based on solid matter) of 0.5 to 13.0% by mass. By setting the content of the above in the range of 1.5 to 6% by mass (Examples 1 to 4, 11 and 13 to 16) with respect to the total mass of the base, the odor of the formulation derived from gelatin can be masked ( It was confirmed that an odor score of 50 or less) and an adhesive strength (stopping distance of 20 to 90 mm) acceptable as a preparation can be obtained. On the other hand, when the gelatin content was 7.5% by mass (Comparative Examples 11 to 14), the adhesive strength was weak (the stopping distance exceeded 90 mm), which was unacceptable as a preparation.

As is clear from the results shown in Table 7, polyvinyl is used as a base having a content (based on solid matter) of methyl acrylate / 2-ethylhexyl acrylate copolymer emulsion of 0.5 to 13.0% by mass. By setting the alcohol (PVA) content in the range of 0.5 to 8% by mass (Examples 1 to 5 and 7 to 10) with respect to the total mass of the base, the odor of the formulation derived from PVA is masked. It was confirmed that it was possible (smell score 50 or less) and that an acceptable adhesive strength as a preparation (stop distance 20 to 90 mm) was obtained. On the other hand, when the PVA content was 10% by mass (Comparative Examples 6 to 9), the adhesive strength was so strong that the pain at the time of peeling became unacceptable (stop distance less than 20 mm).

(Example 17)
First, 2 parts by mass of gelatin, 5 parts by mass of polyvinyl alcohol (PVA), and 10 parts by mass of methyl acrylate / 2-ethylhexyl acrylate copolymer emulsion ("Nicazole TS-620" manufactured by Nippon Carbide Industries, Ltd.) (based on solids). ), 1 part by mass of L-menthylglyceryl ether, 1 part by mass of sodium polyacrylate (PANa), 0.1 part by mass of magnesium silicate, 2 parts by mass of glycol salicylate, 1 part by mass of tocopherol acetate, 1 part by mass of polyethylene glycol monostearate. 76.9 parts by mass of purified water and 76.9 parts by mass of purified water were mixed and stirred to prepare a plaster containing a base and a drug.

The obtained plaster was uniformly spread on a release liner so as to be 7 g per one poultice (140 mm × 100 mm). A support was immediately laminated on the support to obtain a poultice. The adhesive test and the sensory test were performed on this poultice. The results are shown in Table 8.

As is clear from the results shown in Table 8, when the drug is contained in the poultice using L-mentylglyceryl ether as the cooling agent (that is, the poultice having a plaster layer containing the base and the drug). ), But by blending a poly (methyl acrylate / 2-ethylhexyl acrylate) copolymer in the plaster layer, the unpleasantness generated from gelatin and polyvinyl alcohol while maintaining the adhesive strength of the plaster layer. It was confirmed that the odor was suppressed.

As described above, according to the present invention, even when L-menthylglyceryl ether is used as the cooling agent, the application is suppressed from generating an unpleasant odor while maintaining the adhesive strength of the base. It becomes possible to provide an agent base.

Therefore, since the patch obtained by the present invention has a plaster layer formed by using such a base, it can be used for a long time without feeling an unpleasant odor such as a pungent odor or a preparation odor. It is useful in that it can be done.

Claims (4)

A method for producing a base containing gelatin, polyvinyl alcohol, 2-ethylhexyl acrylate copolymer, and L-menthylglyceryl ether.
With respect to the total mass of the base
The gelatin content is 1.5 to 6% by mass.
The content of the polyvinyl alcohol is 0.5 to 8% by mass.
So that the content of the methyl acrylate / 2-ethylhexyl acrylate copolymer is 0.5 to 13% by mass.
A method for producing a base for a patch, which comprises mixing gelatin, polyvinyl alcohol, 2-ethylhexyl acrylate copolymer, and L-menthylglyceryl ether. The method for producing a base for a patch according to claim 1, wherein at least one pressure-sensitive adhesive selected from the group consisting of polyacrylic acid and a neutralized polyacrylic acid is further mixed. A method for producing a patch having a plaster layer containing a base and a drug on a support.
A patch that prepares the base by the method according to claim 1 or 2, forms the plaster layer containing the base and the drug, and laminates the support on the plaster layer. Manufacturing method. The method for producing a patch according to claim 3, wherein a plaster containing the base and the drug is prepared, and the plaster is spread on a release liner to form the plaster layer.